Essential tremor: Is the word “essential” really essential?

Essential tremor (ET) is among the common movement disorders. A surge in research in recent years has considerably improved our understanding of disease etiology and pathogenesis, and its associated clinical phenomenology and natural history. With this progress have emerged a multitude of new questions and conundrums and newly proposed terminologies. Amidst these various related discussions, it is worth revisiting the essence of the nomenclature, “essential tremor”, to assess how well it continues to fit the growing understanding of this entity.Here we revisit the historical underpinnings of the nomenclature, its accuracy, pitfalls of eliminating the word, and advantages of removing the word. There are two primary historical bases for using the word “essential”: (i) idiopathic or unclear etiology, (ii) a unitary (single-featured) trait perceived as a constitutional feature. Numerous studies indicate that ET is neither truly idiopathic nor is fully isolated, making the use of “essential” technically incorrect. There are pitfalls and advantages of eliminating the term “essential” and both are succinctly described in this article. Yet in the absence of any flawless alternatives at present, we conclude that it is preferable for now to persist with “essential” tremor, thereby respecting the historical continuity of this one-and-a-half-century old nomenclature.     

Tremor—some controversial aspects

The commonest cause of pathological tremor is essential tremor (ET). However, it has proved difficult to identify genetic mutations causing ET, particularly because other causes of tremor continue to be misdiagnosed as ET. Whether subjects with dystonia or Parkinson's disease (PD) carry an increased genetic risk of developing ET, or vice versa, is controversial. In addition, the notion of a separate disorder of benign tremulous parkinsonism (BTP) has been debated. This article gives a selective viewpoint on some areas of uncertainty and controversy in tremor. © 2010 Movement Disorder Society     

The Italian tremor Network (TITAN): rationale,design and preliminary findings

Neurological Sciences - The recently released classification has revised the nosology of tremor, defining essential tremor (ET) as a syndrome and fueling an enlightened debate about some newly...     

Self-reported depression and anti-depressant medication use in essential tremor: cross-sectional and prospective analyses in a population-based study

There are few data on the co-morbidity of essential tremor (ET) with depression. To assess the associations of ET with self-reported depression and antidepressant medication use. In a population-based study in central Spain, participants were evaluated at baseline (1994–1995) and 3 years later. Self-reported depression and use of antidepressant medications were evaluated at each assessment. In cross-sectional analyses, prevalent ET cases were twice more probably than controls to report depression [103 (43.8%) of 235 cases versus 1137 (26.0%) of 4379 controls; adjusted odds ratio (OR) 2.20, 95% confidence interval (CI) 1.66–2.93, P  < 0.001] and three times more probably to be taking antidepressant medications [16 (6.8%) cases versus 113 (2.6%) controls; adjusted OR 3.33, 95% CI 1.91–5.82, P  = 0.001]. In prospective analyses, baseline self-reported depression (adjusted RR 1.78, 95% CI 1.11–2.89, P  = 0.018) and, perhaps, baseline use of antidepressant medication (adjusted RR 1.90, 95% CI 0.59–6.05, P  = 0.28) were associated with incident ET. Rather than being totally benign, ET seems to be associated with a mood disorder. Furthermore, as well as being a secondary response to disease manifestations, this mood disorder may be a primary feature of the underlying disease.     

Different clinical features of essential tremor: a 200-patient study

Two hundred consecutive patients affected by essential tremor (ET), referred to the Movement Disorders Center of the University of Bologna between January 1977 and December 1981, were studied to identify the different clinical features of this disorder, and its associated neurological signs. In this series, 169 patients suffered from typical essential tremor (TET); in the other 31 cases uncommon clinical features were detected: 25 presented postural, action and rest tremor (continuous tremor: CT); 5 had orthostatic tremor (OT) and 1 was affected by writing tremor (WT). Buccolinguofacial dyskinesias (BLFD) were associated with ET in 19 cases; 2 presented dystonia, and in 6 mild extrapyramidal signs were detected. Uncommon types of tremor: ET plus BLFD and ET associated with extrapyramidal signs had an higher incidence in older people. No patient developed Parkinson's disease (PD) during the follow-up period (2-5 years).     

Essential tremor

Essential tremor (ET) is one of the most common movement disorders. Although often considered a monosymptomatic disorder (postural and kinetic tremor), ET has more recently been considered a more heterogeneous syndrome, with motor and nonmotor features. The diagnosis is clinical and pharmacologic and surgical therapies exist. ET is frequently misdiagnosed as Parkinson disease or dystonia. The traditional notion of ET as a benign disorder has been challenged by those who view ET as a slowly progressive neurodegenerative disorder.     

Further evidence of genetic heterogeneity in familial essential tremor

Familial essential tremor (FET) is a common hereditary movement disorder with phenotypic variability and genetic heterogeneity. To date, linkage analyses revealed three loci associated to essential tremor (ET) (ETM1 on 3q13, ETM2 on 2p22-25, and a locus on 6p23). We performed a genetic analysis of these candidate chromosomal regions in a fifth-generation Italian kindred with autosomal-dominant ET. Of the 22 clinically evaluated family members, nine were affected by ET. The genetic study indicates that the ET in this family is not associated to any of the known ET loci. These findings support evidence of further genetic heterogeneity for such disease.     

Essential tremor

Essential tremor (ET) is one of the most common neurological diseases; although it is a disease about which we are only beginning to develop an understanding. Effective treatment options for the disorder are severely limited. The traditional view of ET as a benign, familial, monosymptomatic disorder is being replaced by one of ET as a disease or family of diseases with aetiological, clinical, and pathological heterogeneity. Recent identification of putative environmental toxins linked to ET provide hope for disease prevention through a reduction in exposure to risk factors. Pathological and genetic studies will yield new insights into disease pathogenesis and mechanisms, which may result in the development of more effective symptomatic therapies developed with an understanding of the disease biology. These insights also have the potential to form the basis for neuroprotective therapies.     

Study of possible factors associated with age of onset in essential tremor.

Factors associated with the age of onset of essential tremor (ET) have not been studied in detail. Identification of modifiable factors could lead to strategies to delay disease onset and identification of nonmodifiable factors would be useful while counseling at risk individuals. The objective of this study was to identify factors associated with age of onset of tremor in ET. One hundred ninety-five ET cases were enrolled in an environmental epidemiological study. Clinical questionnaires included questions on age of onset, demographics (age, sex, race, education), early-life exposures (birth order, childhood household size), exposures prior to tremor onset (head trauma, well water, rural living, estrogen replacement therapy), and family history. In unadjusted analyses, age of onset was associated with family history of tremor (40.9 +/- 22.0 years for cases with a family history of tremor vs. 57.3 +/- 18.4 years for cases without a history; P < 0.001), history of head trauma, younger current age, greater tremor severity, and white race. Ninety-one percent of cases with onset before age 20 years had a family history of tremor. Age ofonset was not associated with other variables of interest (e.g., sex, well water, rural living). In an adjusted linear regression model, age of tremor onset was strongly associated with family history of tremor (P < 0.001). The familial form of ET is characterized by an earlier age of onset than the sporadic form. This study did not detect any other exposures that modified the age of onset of ET. Follow-up studies are needed to examine additional factors of potential interest.     

Validity of family history in essential tremor

In this study, we found the sensitivity and specificity of family history data given by essential tremor (ET) patients to be 43.3% and 94.4%. Compared to relatives with less severe tremor (tremor score <24), those with more severe tremor (tremor score 24) were more likely to be identified by the ET probands (8/8 vs. 5/22, p=0.001, chi2 14.3). Our study suggests that family history information reported by ET patients was inaccurate, and poorly validated. Clinical and genetic studies in ET should take the limitation of family history data into consideration.     

Essential tremor centralized brain repository: diagnostic validity and clinical characteristics of a highly selected group of essential tremor cases.

We studied essential tremor (ET) cases enrolled in the Essential Tremor Centralized Brain Repository to (1) assess the validity of their diagnoses and (2) characterize the clinical features in a group of highly selected cases who might reflect a far end of the disease spectrum. Our over-arching goal was to provide a perspective of ET that complements that derived from population-based and clinic-based studies. Based on a history and videotaped examination, 94 of 100 ET cases had their diagnoses confirmed; most of the remainder had Parkinson's disease. When compared with ET cases ascertained through populations and clinics, a large proportion had been prescribed medication for tremor (87.2%), had a family history of tremor (88.3%), had rest tremor (33.0%), or had neck tremor (60.6%). One patient had facial tremor, which has not been reported previously. As has been reported once before, a large proportion wore hearing aids (26.9% of the 67 participants age>or=70). In summary, diagnostic validity was high. In terms of their clinical characteristics, the high proportion of cases with severe tremor and varied disease manifestations (neck tremor, rest tremor) make these cases a valuable resource in pathological studies; the high proportion with familial tremor would provide an enriched sample for genetic studies.     

A new twist for stopping the shakes? Revisiting GABAergic therapy for essential tremor.

Aside from physiological tremor, essential tremor (ET) is by far the most common cause of tremor in humans, affecting large numbers of individuals in every human population. The crude prevalence of ET has been conservatively estimated to be between 0.4% and 3.9%, although some estimates of the prevalence of ET among the elderly are higher than 20%. Essential tremor is the most prevalent adult-onset movement disorder, and is also regarded as one of the most common neurological disorders of adults, with a prevalence that is similar to or greater than that of stroke, Alzheimer disease, migraine headache, and lumbosacral pain syndromes. Essential tremor is as much as 20 times more prevalent than Parkinson disease.     

Isolated tremor and disruption of the nigrostriatal dopaminergic system: an 18F-dopa PET study.

We measured striatal 18F-dopa influx constants (Ki) for 20 patients with isolated, predominantly postural, tremor (eight familial, 12 sporadic) and 11 with predominantly rest tremor. Results were compared with 30 controls and 16 Parkinson's disease (PD) patients. The eight familial essential tremor (ET) patients had normal striatal 18F-dopa uptake. Two of the 12 sporadic postural tremor patients had subnormal putamen 18F-dopa Ki, one (who later became akinetic) falling in the PD range. The mean putamen 18F-dopa uptake of the 11 rest tremor patients was reduced to PD levels (51% of normal). Our findings argue against an association between ET and PD, but support the existence of a "benign" tremulous variant of PD. The presence of low-amplitude rest tremor, cogwheel rigidity, reduced arm swing, and short tremor duration was not a useful predictor of nigral dysfunction in patients with postural tremor. In contrast, patients with predominantly rest tremor, particularly with onset in the leg, consistently showed reduced putamen 18F-dopa uptake.     

Essential tremor: emerging views of a common disorder

Essential tremor (ET) is the most prevalent tremor disorder. ET has traditionally been viewed as a monosymptomatic disorder characterized by a kinetic arm tremor, but this definition is gradually being replaced. The clinical spectrum has come to include several motor features, including tremor and ataxia, and several non-motor features, including possible cognitive impairment and personality disturbances. Postmortem studies are revealing several different patterns of pathology. The emerging view is that ET might be a family of diseases, unified by the presence of kinetic tremor, but further characterized by etiological, clinical and pathological heterogeneity. Effective pharmacological treatments for the disorder remain limited, although new insights into disease mechanisms might result in more-effective therapies. In addition, recent investigations of environmental toxicants that might be linked to ET open the way towards primary disease prevention through a reduction in exposure to these factors.     

Essential tremor in Papua, New Guinea.

The clinical features of 175 cases of essential tremor are related. This disorder is prevalent among a population of the Eastern Highlands of Papua New Guinea. It affects predominantly women in middle and old age; only 27 per cent of the cases were males. The disorder is slowly progressive and significant disability appears in elderly women when the trunk muscles are involved. Epidemiological studies have shown that the presence of tremor can be correlated with linguistic distinctions between high and low prevalence populations. Although only 30 patients reported a first degree relative with tremor, the syndrome would seem to stem from a genetic predisposition. In a number of patients essential tremor appeared to be associated with Parkinson's disease.     

Essential tremor and cerebellar dysfunction: abnormal ballistic movements

BACKGROUND: Clinical characteristics reminiscent of cerebellar tremor occur in patients with advanced essential tremor. Ballistic movements are known to be abnormal in cerebellar disease. The hypothesis was proposed that ballistic movements are abnormal in essential tremor, reflecting cerebellar dysfunction. OBJECTIVE: To elucidate the role of the cerebellum in the pathophysiology of essential tremor. METHODS: Kinematic parameters and the triphasic electromyographic (EMG) components of ballistic flexion elbow movements were analysed in patients assigned to the following groups: healthy controls (n = 14), pure essential postural tremor (ET(PT); n = 17), and essential tremor with an additional intention tremor component (ET(IT); n = 15). RESULTS: The main findings were a delayed second agonist burst (AG(2)) and a relatively shortened deceleration phase compared with acceleration in both the essential tremor groups. These abnormalities were most pronounced in the ET(IT) group, which had additional prolongation of the first agonist burst (AG(1)) and a delayed antagonist burst (ANT). CONCLUSIONS: Abnormalities of the triphasic pattern and kinematic parameters are consistent with a disturbed cerebellar timing function in essential tremor. These abnormalities were most pronounced in the ET(IT) group. The cerebellar dysfunction in essential tremor could indicate a basic pathophysiological mechanism underlying this disorder. ET(PT) and ET(IT) may represent two expressions within a continuous spectrum of cerebellar dysfunction in relation to the timing of muscle activation during voluntary movements.     

Essential tremor--a neurodegenerative disorder associated with cognitive defects?

In the past decade, the hypothesis that essential tremor is a monosymptomatic tremorogenic disorder has been questioned. New clinical, neuroimaging, electrophysiological and pathological studies indicate that essential tremor is associated with subtle neurological deficits and could be considered a slowly progressive neurodegenerative disorder. The aim of this Review is to describe the nonmotor neurological symptoms that are commonly associated with essential tremor, and highlight the cognitive deficits associated with this condition. Several clinical studies have demonstrated that essential tremor is associated with mild deficits in attention, executive functions, memory and, possibly, other cognitive processes. Population-based surveys have confirmed that dysfunction in these cognitive domains affects patients both with severe and mild essential tremor. Clinical studies have also indicated that cognitive deficits associated with essential tremor are progressive and that patients with this condition have an increased risk of dementia. Mood and cognitive deficits commonly observed in patients with essential tremor are similar to symptoms of cerebellar cognitive affective syndrome. Further evidence is required from prospective studies to support the interpretation that essential tremor is a slowly progressive neurodegenerative disorder.     

Common misdiagnosis of a common neurological disorder: how are we misdiagnosing essential tremor?

BACKGROUND: As a common neurological disorder, the diagnosis of essential tremor (ET) is considered routine. Despite this, previous work suggests that misdiagnoses may be common. Among other things, these misdiagnoses can lead to treatment errors. OBJECTIVES: To estimate how often other tremor disorders are misdiagnosed as ET and to identify factors that increase the odds of misdiagnosing ET and to precisely quantify the extent to which they do so. DESIGN: Seventy-one consecutive patients underwent an evaluation at the Neurological Institute of New York, New York, between January 1, 2000, and December 31, 2005; these patients had a pre-evaluation diagnosis of ET. The criteria for ET were adapted from the consensus statement of the Movement Disorder Society. RESULTS: Twenty-six patients (37%) were misdiagnosed as having ET ("false ET"). Their true diagnoses were Parkinson disease (11 patients [15%]), dystonia (6 patients [8%]), Parkinson disease with ET (5 patients [7%]), and other disorders (4 patients [6%]). Factors associated with misdiagnosed ET included unilateral arm tremor (odds ratio, 10.5; 95% confidence interval, 1.2-95.4; P=.02), spooning of the hands and other dystonic postures (odds ratio, 16.3; 95% confidence interval, 4.0-66.4; P<.001), and other unusual features (isolated thumb tremor, isolated leg tremor, and non-rhythmic tremor) (odds ratio, 49.4; 95% confidence interval, 2.7-895.0; P<.001). CONCLUSIONS: About 1 in 3 patients with tremor was misdiagnosed as having ET, with the most frequent false diagnoses being Parkinson disease and dystonia. Several factors that increased the odds of misdiagnosing ET were identified. These factors could be incorporated into improved diagnostic algorithms.     

Benign essential tremor. A clinical survey of 82 patients from Campania, a region of southern Italy

We report a clinical survey of 82 patients with benign essential tremor (ET). Sixty five patients had a positive family history. Onset age showed two peaks before 20 years and in the sixth decade. Segregation analysis confirmed an autosomal dominant inheritance. Head tremor occurred mainly in aged women, mental symptoms occurred mainly in subjects with a low onset age and a disabling tremor. An early onset age was not related to paternal or maternal transmission. In one family ET was associated with retinitis pigmentosa and ichthyosis.     

Long duration asymmetrical postural tremor is likely to predict development of Parkinson's disease and not essential tremor: clinical follow up study of 13 cases

BACKGROUND: Patients presenting with asymmetrical postural tremor with or without mild rest tremor may be diagnosed as having essential tremor (ET), although there is considerable diagnostic uncertainty as to the long term outcome of these patients. OBJECTIVE: In this study, retrospective observations were made on 13 patients presenting originally with asymmetrical postural tremor, initially thought to have ET based on tremor characteristics, alcohol responsiveness, and family history but who subsequently met the criteria of Parkinson's disease (PD). METHODS: The patients were observed and followed up clinically with ancillary imaging using dopamine transporter SPECT scan or levodopa challenge tests in some cases. The diagnosis at original presentation with postural tremor was made with retrospective case note review. RESULTS: After a variable and long latent period all patients developed additional signs suggesting a clinical diagnosis of PD although picking up an initial label of ET. CONCLUSIONS: We suggest exercising caution regarding a diagnosis of ET in patients presenting with late onset asymmetrical postural tremor even if there is no rest tremor. Alcohol sensitivity of tremor, family history of tremor, or responsiveness to beta blockers may not be helpful in diagnosing ET in these cases and some may develop PD in the long term.